title: Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells.
abstract: BACKGROUND
  Helicobacter pylori infection induces a biased T helper type 1 (Th1) response that produces IFN-gamma and Fas ligand (FasL). Th1 cytokines are associated with apoptosis in the gastric epithelial cells.
  
  
  OBJECTIVE
  We aimed to define the role of the recently cloned IL-18, a IFN-gamma inducing factor, in gastric mucosal injury induced by H. pylori infection.
  
  
  METHODS
  Twenty-seven gastric ulcer (GU) patients and 20 functional dyspepsia (FD) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used for histological examination, H. pylori culture and in-situ stimulation for 48 h in the presence of 10 microg/ml phytohemagglutinin-P. IL-18, IFN-gamma, and soluble FasL (sFasL) levels in culture supernatants were assayed by the enzyme-linked immunosorbent assay method. IL-18, IL-1beta-converting enzyme (ICE) and caspase-3 were evaluated by western blotting in gastric cancer cell lines (MKN45) cocultured with H. pylori.
  
  
  RESULTS
  All 27 GU patients and ten out of 20 FD patients were found to be H. pylori-positive, whereas ten FD patients were H. pylori-negative. Antral mucosal tissues from H. pylori-positive FD patients contained (P<0.01) higher levels of IL-18, IFN-gamma, and sFasL than those from uninfected FD patients. IL-18, IFN-gamma, and sFasL levels at the ulcer site were significantly (P<0.01) higher than those at distant sites in the antrum. A significant relationship was seen between IL-18 and IFN-gamma levels at the ulcer site (r=0.7, P<0.01). H. pylori eradication led to a significant decrease in the levels of IL-18, IFN-gamma, and sFasL at the ulcer site. Western blotting showed that IL-18, ICE, and caspase-3 were activated in gastric cancer cell lines cocultured with H. pylori.
  
  
  CONCLUSIONS
  This study suggests that H. pylori infection enhanced mucosal injury by stimulating a Th1 response, which was mediated by IL-18 upregulation as well as activation of ICE and caspase-3.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya Memorial Hospital, Showa-ku, Nagoya, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Osamu
authors.initials: O
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ishikawa
authors.forename: Motofusa
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Ina
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohmiya
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Niwa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004415:Dyspepsia / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D053222:Fas Ligand Protein / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D020382:Interleukin-18 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D013276:Stomach Ulcer / Q000276:immunology / Q000382:microbiology*; D015854:Up-Regulation
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D020382:Interleukin-18; D007371:Interferon-gamma; D053148:Caspase 3; D020170:Caspase 1